chr5-148063797-G-A

Position:

• chr5-148063797-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000521206.5(SPINK5):​c.-182-66G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0427 in 567,076 control chromosomes in the GnomAD database, including 878 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.034 (149 hom., cov: 32)
  • Exomes 𝑓: 0.046 (729 hom.)
• Consequence: SPINK5 ENST00000521206.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.72

Genes affected

SPINK5 (HGNC:15464): (serine peptidase inhibitor Kazal type 5) This gene encodes a multidomain serine protease inhibitor that contains 15 potential inhibitory domains. The encoded preproprotein is proteolytically processed to generate multiple protein products, which may exhibit unique activities and specificities. These proteins may play a role in skin and hair morphogenesis, as well as anti-inflammatory and antimicrobial protection of mucous epithelia. Mutations in this gene may result in Netherton syndrome, a disorder characterized by ichthyosis, defective cornification, and atopy. This gene is present in a gene cluster on chromosome 5. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2015]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 5-148063797-G-A is Benign according to our data. Variant chr5-148063797-G-A is described in ClinVar as [Benign]. Clinvar id is 1165060.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.116 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPINK5	ENST00000521206.5	c.-182-66G>A		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.0338 AC: 5138 AN: 151980 Hom.: 149 Cov.: 32

Gnomad AFR AF: 0.00694

Gnomad AMI AF: 0.0143

Gnomad AMR AF: 0.0538

Gnomad ASJ AF: 0.0320

Gnomad EAS AF: 0.125

Gnomad SAS AF: 0.0666

Gnomad FIN AF: 0.0574

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0335

Gnomad OTH AF: 0.0239

GnomAD4 exome AF: 0.0460 AC: 19072 AN: 414978 Hom.: 729 AF XY: 0.0459 AC XY: 10087 AN XY: 219976

Gnomad4 AFR exome AF: 0.00676

Gnomad4 AMR exome AF: 0.0545

Gnomad4 ASJ exome AF: 0.0298

Gnomad4 EAS exome AF: 0.162

Gnomad4 SAS exome AF: 0.0610

Gnomad4 FIN exome AF: 0.0539

Gnomad4 NFE exome AF: 0.0327

Gnomad4 OTH exome AF: 0.0361

GnomAD4 genome AF: 0.0338 AC: 5144 AN: 152098 Hom.: 149 Cov.: 32 AF XY: 0.0367 AC XY: 2725 AN XY: 74328

Gnomad4 AFR AF: 0.00692

Gnomad4 AMR AF: 0.0540

Gnomad4 ASJ AF: 0.0320

Gnomad4 EAS AF: 0.124

Gnomad4 SAS AF: 0.0675

Gnomad4 FIN AF: 0.0574

Gnomad4 NFE AF: 0.0335

Gnomad4 OTH AF: 0.0237

Alfa AF: 0.0316 Hom.: 95

Bravo AF: 0.0312

Asia WGS AF: 0.0850 AC: 296 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Ichthyosis linearis circumflexa Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 11, 2023

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 26, 2018

This variant is associated with the following publications: (PMID: 19534795) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.053
DANN	Benign	0.67

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2287774; hg19: chr5-147443360;